Recent studies into the molecular biology of aging brain have stressed alterations in metabolism and disposition of nucleic acids and neurotransmitters in whole brain and brain regions. The metabolism and disposition of the brain polyamines, spermidine and spermine, may comprise an important link to the reputed alterations in nucleic acids and neurotransmitters with age. Research from this laboratory has documented a significant increase in spermidine concentrations within some brain regions without a concomitant increase in spermine. Since S-adenosyl-L-methionine (SAM) is required for the synthesis of spermidine, as well as being the methyl donor for post-transcriptional methylation of nucleic acids and neurotransmitters including histamine, perhaps increased spermidine synthesis with age alters the metabolism and disposition of SAM. Brain regional polyamine, histamine, and SAM metabolism and the activity and disposition of related enzymes will be investigated in adult and aged rats in order to evaluate metabolic control mechanisms with respect to SAM in the aging brain. The relationship of polyamine turnover to SAM metabolism and the activity of histamine-N-methyl transferase will be focused on the hypothalamus, a brain region in which the proposed interaction of these metabolic-control molecules may significantly influence organismic aging. During the first year of this research, a sensitive enzymatic-isotopic assay was developed for the evaluation of SAM levels in brain regions. An unexpected preliminary finding in adult rat brain regions is that SAM may exist in "free" and "bound" pools. Since a proportionate change during aging in the relationship of "free" and "bound" pools of SAM could significantly influence transmethylations, current work has been directed towards better defining these pools in adult rats before investigating the situation in aged rats.